Part 1
News Release: November 24, 2003
Positive Results from Final Exenatide Pivotal Study Mark Successful Completion of Phase 3
Statistically Significant Improvements in Glucose Control and Weight Seen Across All Long-term Studies
SAN DIEGO and INDIANAPOLIS, Nov. 24 -- Amylin Pharmaceuticals, Inc., (Nasdaq: AMLN ) and Eli Lilly and Company (NYSE: LLY ) today announced positive results from the final Phase 3 pivotal study of exenatide (synthetic exendin-4), marking the conclusion of the long-term human clinical trials required for a regulatory submission to the U.S. Food and Drug Administration. All of the pivotal studies met the primary glucose control endpoint as measured by hemoglobin A1c (A1C). A1C is a measure that reflects average glucose levels over the prior 3 to 4 month period. The average reduction in A1C across the Phase 3 program in patients completing the studies on the highest dose of exenatide (10 micrograms twice daily) was approximately one percent. Additionally, approximately 40 percent of these patients achieved A1C measurements of 7 percent or less. On average, subjects in the Phase 3 program on the highest dose of exenatide also showed statistically significant reductions in body weight of approximately two kilograms. The most common adverse event was mild to moderate, transient nausea.
"Improving glucose control without weight gain is a significant challenge for people with type 2 diabetes," said Orville G. Kolterman, MD, Senior Vice President, Clinical Affairs for Amylin Pharmaceutical, Inc. "We are pleased to see these reductions in A1C in the context of weight loss with no increased risk of severe hypoglycemia."
"We believe the data from the Phase 3 program provide a solid base for a regulatory submission to the FDA, currently projected for mid-2004," said Elizabeth Klimes, President, Diabetes Care and Growth Disorders at Lilly. "The results from the Phase 3 pivotal studies suggest exenatide could provide an important new treatment tool for people with diabetes struggling to reach target glucose levels but failing with current oral therapies."
Key Study Details From the Third Exenatide Pivotal Trial
Reductions in A1C in the third exenatide pivotal trial were similar to those observed in the first two studies announced in August and November 2003. Despite having failed to reach treatment goals on two oral agents prior to entering this study, 34 percent of subjects completing the study on the highest dose of exenatide (10 micrograms twice daily) reduced their A1C levels to less than or equal to 7 percent. The subjects receiving the highest dose of exenatide also showed statistically significant reductions in body weight.
Of the 734 randomized subjects, approximately two-thirds received exenatide and one-third received placebo. Those on active drug received an introductory 5-microgram dose of exenatide for one month, given by subcutaneous injection twice a day at breakfast and dinner. This was followed by six months of exposure to doses of either 5 micrograms or 10 micrograms given twice a day at breakfast and dinner.
In order to more effectively evaluate sulfonylurea-related hypoglycemia, patients in each treatment group were further randomized into two groups. Patients in the first group were instructed to maintain their maximally effective dose of sulfonylurea unless hypoglycemia occurred, at which point they were instructed to reduce their dose of sulfonylurea. Patients in the second group reduced their sulfonylurea dose before starting study medication, and were later instructed to titrate their sulfonylurea dose to maximize glucose control.
As expected, rates of mild to moderate hypoglycemia were higher in patients in the first group who maintained their maximally effective dose of sulfonylurea at initiation of exenatide. In this group, patients treated with the highest dose of exenatide showed statistically significant reductions in A1C compared to placebo and a 35 percent incidence of mild to moderate hypoglycemia. In contrast, the placebo arm, with a slight increase in A1C, had an incidence of mild to moderate hypoglycemia of 15 percent. Patients in the second group, who reduced their sulfonylurea dose prior to initiation of exenatide, ended the study with a significant reduction in A1C and a 21 percent incidence of mild to moderate hypoglycemia, compared to 10 percent on placebo. No subjects withdrew from the study due to hypoglycemia. One subject reported a single episode of severe hypoglycemia while receiving the 5 microgram dose of exenatide. No severe hypoglycemia was observed in patients receiving 10 micrograms of exenatide. |
